The long-term objectives are to discover drugs for the treatment of central nervous system (CNS) injuries and disorders, and to discover fundamental new knowledge about the ability to generate human neurons, for application to neurodegenerative diseases. To achieve these goals, conditionally-immortalized human progenitor CNS lines will be developed. Currently, CNS drug development is carried out with rodent cells due to the lack of human neuronal CNS lines and primary tissue; the results are then extrapolated to humans, with the caveat that species differences may exist. Clonal human CNS lines will provide infinite, homogeneous sources of material for CNS drug discovery. Furthermore, these lines will provide information about the capacity of neuronal progenitor cells for proliferation and differentiation. The specific aims are to develop and characterize human CNS lines from specific regions of the brain and spinal cord, and to develop drug assays using these lines. Glutamate, serotonin, nicotinic and GABA receptors will be the focus of these assays because of their central roles in Alzheimer's and Parkinson's diseases, epilepsy and ischemic brain damage due to stroke, myocardial infarction and traumatic head injury. PROPOSED COMMERCIAL APPLICATION: The potential commercial application of the research is that a renewable source of human neurons would be available for screening CNS drug candidates on neurotransmitter receptors.